Disease-Modifying Therapies in Frontotemporal Lobar Degeneration

B.      Bigni; E.      Premi; A.      Pilotto; A.      Padovani; B.      Borroni

Abstract

Frontotemporal Lobar Degeneration (FTLD) is characterized by behavioral changes, executive dysfunctions, and language impairment, sustained by different neuropathological patterns. The collective efforts of clinical, pathological and genetic studies have recently opened new insights into the underpinnings of pathological mechanisms of this complex disorder. Different types of inclusions define the new conceptual framework for FTLD classification. Up to now, Tau (FTLDTau-positive), TAR DNA-binding protein (TDP43, FTLD Tau-negative TDP43-positive) have been recognized as the most frequent neuropathological hallmarks of FTLD. In some clinical cases, monogenic forms are identified, mainly due to Microtubule Associated Protein (MAPT) or Granulin (GRN) mutations.

No treatments for FTLD are available yet, and off-label medications studies testing potential modifying treatments on the basis of neuropathological positive, inhibitors of Tau kinases or manipulation of Tau-processing haploinsuffciency associated with GRN mutations, has been counteracted into pathological processing of TDP-43 and other key-molecules involved and their consequent translocation from nucleus to cytoplasm, and growing number of potential therapeutic targets. In this continuously new findings on molecular targets and modifying therapies in FTLD.

Keywords: Frontotemporal Lobar Degeneration, Frontotemporal Dementia, treatment, therapies, Tau, Progranulin, Microtubule Associated Protein (MAPT), Granulin (GRN) mutations, haploinsuffciency, RNA-binding proteins